Simulation of survivorship bias in observational studies on plasma to red blood cell ratios in massive transfusion for trauma

Department of Anaesthesia and Intensive Care, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, China.
British Journal of Surgery (Impact Factor: 5.21). 01/2012; 99 Suppl 1(S1):132-9. DOI: 10.1002/bjs.7732
Source: PubMed

ABSTRACT Observational studies on injured patients requiring massive transfusion have found a survival advantage associated with use of equivalent number of units of fresh frozen plasma (FFP) and packed red blood cells (RBCs) compared with use of FFP based on conventional guidelines. However, a survivorship bias might have favoured the higher use of FFP because patients who died early never had the chance to receive sufficient FFP to match the number of RBC units transfused.
A Markov model using trauma data from local hospitals was constructed and various FFP transfusion scenarios were applied in Monte Carlo simulations in which the relative risk of death associated with exposure to high FFP transfusion was set at 1.00, so that the FFP : RBC ratio had no influence on mortality outcome.
Simulation results showed that the relative risk associated with exposure to high FFP transfusion was less than 1.00 (0.33-0.56 based on programmed delays in achieving an FFP : RBC ratio of 1 : 1-2), thus demonstrating a survivorship bias in favour of FFP : RBC equal to or more than 1 : 1-2 in certain observational trauma studies. This bias was directly proportional to the delay in achieving a FFP : RBC ratio of 1 : 1-2 during resuscitation.
Some observational studies comparing low and high FFP administration in injured patients requiring massive transfusion probably involve survivorship bias that inflates or creates a survival advantage in favour of a higher FFP : RBC ratio.

Download full-text


Available from: Calvin S H Ng, Sep 01, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Observational studies on transfusion in trauma comparing high versus low plasma:erythrocyte ratio were prone to survivor bias because plasma administration typically started later than erythrocytes. Therefore, early deaths were categorized in the low plasma:erythrocyte group, whereas early survivors had a higher chance of receiving a higher ratio. When early deaths were excluded, however, a bias against higher ratio can be created. Survivor bias could be reduced by performing before-and-after studies or treating the plasma:erythrocyte ratio as a time-dependent covariate.We reviewed 26 studies on blood ratios in trauma. Fifteen of the studies were survivor bias-unlikely or biased against higher ratio; among them, 10 showed an association between higher ratio and improved survival, and five did not. Eleven studies that were judged survivor bias-prone favoring higher ratio suggested that a higher ratio was superior.Without randomized controlled trials controlling for survivor bias, the current available evidence supporting higher plasma:erythrocyte resuscitation is inconclusive.
    Anesthesiology 03/2012; 116(3):716-28. DOI:10.1097/ALN.0b013e318245c47b · 6.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hemorrhage remains a major cause of potentially preventable deaths. Trauma and massive transfusion are associated with coagulopathy secondary to tissue injury, hypoperfusion, dilution, and consumption of clotting factors and platelets. Concepts of damage control surgery have evolved prioritizing early control of the cause of bleeding by non-definitive means, while hemostatic control resuscitation seeks early control of coagulopathy. Hemostatic resuscitation provides transfusions with plasma and platelets in addition to red blood cells in an immediate and sustained manner as part of the transfusion protocol for massively bleeding patients. Although early and effective reversal of coagulopathy is documented, the most effective means of preventing coagulopathy of massive transfusion remains debated and randomized controlled studies are lacking. Viscoelastical whole blood assays, like TEG and ROTEM however appear advantageous for identifying coagulopathy in patients with severe hemorrhage as opposed the conventional coagulation assays. In our view, patients with uncontrolled bleeding, regardless of it´s cause, should be treated with hemostatic control resuscitation involving early administration of plasma and platelets and earliest possible goal-directed, based on the results of TEG/ROTEM analysis. The aim of the goal-directed therapy should be to maintain a normal hemostatic competence until surgical hemostasis is achieved, as this appears to be associated with reduced mortality.
    Scandinavian Journal of Trauma Resuscitation and Emergency Medicine 07/2012; 20(1):47. DOI:10.1186/1757-7241-20-47 · 1.93 Impact Factor
  • Source
    Anaesthesia 01/2013; 68(2):126-130. · 3.85 Impact Factor
Show more